20 Apr PIM Kinase Inhibitors May Offer New Melanoma Therapeutic Target
Medical Research: What is the background for this study? What are the main findings?
Dr. Vulture: Our goal was to identify new drugs with anti-melanoma activity but with minor effects on normal cells. We screened structurally distinct kinase inhibitors first, against multiple cell lines and normal cells, and identified the organometallic compound SM200 as being the most effective and selective molecule, capable of halting melanoma cell growth and invasion. Further characterization of SM200 indicated that PIM kinases are highly inhibited by this compound compared to other targets. We then confirmed the contribution of PIM kinases to melanoma pathobiology by knockdown studies and by using a clinically available PIM-inhibitor. Encouraging results with PIM kinase inhibition in multiple melanoma models including xenografts suggests that this could be a useful strategy against melanoma.
Medical Research: What should clinicians and patients take away from your report?
Dr. Vulture: We’d like clinicians and patients to know that new targets for melanoma are continuously being identified and evaluated, also we have libraries of compounds that are yet to be fully evaluated for their anti-cancer properties. In some cases, we even have clinically approved drugs available that could be repurposed for new applications or for specific patients as part of the precision medicine initiative. We still have many opportunities and resources to improve melanoma patient’s lives.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Vulture: Inhibitors of PIM kinases should be evaluated in combination with current melanoma therapies to determine how they can best benefit patients. Do they synergize with other treatments or should they be scheduled carefully? Do they contribute to reducing tumor growth, metastasis, or preventing drug resistance equally? Ultimately, we would like to add a new group of effective inhibitors to the arsenal of drugs available against advanced melanoma.
AACR abstract April 2015
Adina M. Vultur1, Batool Shannan1, Quan Chen1, Andrea Watters1, Stefan Mollin2, Eric Meggers2, Clemens Krepler1, Michela Perego1, Ling Li1, Phyllis A. Gimotty3, Xiaowei Xu3, Meenhard Herlyn1. 1The Wistar Institute, Philadelphia, PA; 2Philipps University, Marburg, Germany; 3University of Pennsylvania School of Medicine, Philadelphia, PA
MedicalResearch.com Interview with: Adina Vultur, Ph.D. (2015). PIM Kinase Inhibitors May Offer New Melanoma Therapeutic Target